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Eva1 Maintains the Stem-like Character of Glioblastoma-Initiating Cells by Activating the Noncanonical NF-κB Signaling Pathway
| Title: | Eva1 Maintains the Stem-like Character of Glioblastoma-Initiating Cells by Activating the Noncanonical NF-κB Signaling Pathway |
| Other Titles: | Eva1 is a novel GIC regulator |
| Authors: | Ohtsu, Naoki Browse this author | | Nakatani, Yuka Browse this author | | Yamashita, Daisuke Browse this author | | Ohue, Shiro Browse this author →KAKEN DB | | Ohnishi, Takanori Browse this author | | Kondo, Toru Browse this author →KAKEN DB |
| Keywords: | Glioblastoma (GBM) | | GBM-initiating cells (GICs) | | Eva1 | | non-canonical NF-κB |
| Issue Date: | Jan-2016 |
| Publisher: | American Association for Cancer Research |
| Journal Title: | Cancer research |
| Volume: | 76 |
| Issue: | 1 |
| Start Page: | 171 |
| End Page: | 181 |
| Publisher DOI: | 10.1158/0008-5472.CAN-15-0884 |
| PMID: | 26677976 |
| Abstract: | Glioblastoma (GBM)-initiating cells (GICs) are a tumorigenic subpopulation that are resistant to radio- and chemotherapies and are the source of disease recurrence. Therefore, the identification and characterization of GIC-specific factors is critical towards the generation of effective GBM therapeutics. In this study, we investigated the role of Epithelial V-like antigen 1 (Eva1, also known as myelin-like protein Zero like-2) in stemness and GBM tumorigenesis. Eva1 was prominently expressed in GICs in vitro and in stem cell marker (Sox2, CD15, CD49f)-expressing cells derived from human GBM tissues. Eva1 knockdown in GICs reduced their self-renewal and tumor-forming capabilities, whereas Eva1 overexpression enhanced these properties. Eva1-deficiency was also associated with decreased expression of stemness-related genes, indicating a requirement for Eva1 in maintaining GIC pluripotency. We further demonstrate that Eva1 induced GIC proliferation through the activation of the RelB-dependent noncanonical NF-κB pathway by recruiting TRAF2 to the cytoplasmic tail. Taken together, our findings highlight Eva1 as a novel regulator of GIC function and also provide new mechanistic insight into the role of non-canonical NF-κB activation in GIC, thus offering multiple potential therapeutic targets for preclinical investigation in GBM. |
| Type: | article (author version) |
| URI: | http://hdl.handle.net/2115/63977 |
| Appears in Collections: | 遺伝子病制御研究所 (Institute for Genetic Medicine) > 雑誌発表論文等 (Peer-reviewed Journal Articles, etc)
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Submitter: 近藤 亨
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